3-Nitropropionic acid induced in vivo protein oxidation in striatal and cortical synaptosomes: Insights into Huntington's disease

Michael A. La Fontaine, James W. Geddes, Andrea Banks, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

3-Nitropropionic acid (3-NP) administered systemically daily for 4 days to rats inhibits mitochondrial oxidative phosphorylation and induces selective lesions in the striatum in a manner reminiscent of Huntington's disease (HD). To investigate the potential oxidative nature of these lesions, rats were injected with 3-NP (20 mg/kg, i.p. daily for 4 days) and subsequently isolated brain synaptosomal membranes were examined for evidence of oxidative stress. Brain synaptosomal membrane proteins from rats injected with 3-NP exhibited a decreased in W/S ratio, the relevant electron paramagnetic resonance (EPR) parameter used to determine levels of protein oxidation (76% of control), and Western blot analysis for protein carbonyls revealed direct evidence of increased synaptosomal membrane protein oxidation (248% of control). Similar results were obtained in synaptosomes isolated from striatum and from cerebral cortex, demonstrating that the oxidative changes are not restricted to the lesion site. Moreover, increased oxidative stress was evident prior to the appearance of morphological lesions. These data are consistent with the hypothesis that 3-NP-induced striatal lesions, and perhaps those in HD, are associated with oxidative processes. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)356-362
Number of pages7
JournalBrain Research
Volume858
Issue number2
DOIs
StatePublished - Mar 10 2000

Bibliographical note

Funding Information:
This work was supported in part by grants from NIH (AG-05119; AG-10836) [D.A.B.] and (AG-05144; AG-10836) [J.W.G.].

Keywords

  • 3-Nitropropionic acid
  • Huntington's disease
  • Oxidative stress
  • Spin labeling
  • Synaptosomal membrane

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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